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Difficulty: HardInfectious Diseases

A 3232-year-old man comes to the clinic for routine sexually transmitted infection screening. He is currently asymptomatic and has no history of genital ulcers, diffuse rashes, or neurologic symptoms. He reports having unprotected intercourse with a new male sexual partner 22 months ago. He has no known prior history of syphilis or other sexually transmitted infections. Vital signs are within normal limits. Physical examination reveals no oral, genital, or perianal lesions, and no lymphadenopathy is appreciated. The clinic laboratory utilizes the reverse sequence algorithm for syphilis screening. The initial *Treponema pallidum* enzyme immunoassay (EIA) returns reactive. A reflex rapid plasma reagin (RPR) test is nonreactive. Which of the following is the most appropriate next step in management?

  1. Perform a Treponema pallidum particle agglutination (TP-PA) testAnswer
  2. B
    Administer a single dose of intramuscular benzathine penicillin G
  3. C
    Administer three doses of intramuscular benzathine penicillin G
  4. D
    Reassure the patient that the enzyme immunoassay result is a false positive
  5. E
    Repeat the rapid plasma reagin (RPR) test in 6 months

Answer

The most appropriate next step is to perform a second, different treponemal test, specifically the Treponema pallidum particle agglutination (TP-PA) test.
The correct answer is to perform a Treponema pallidum particle agglutination (TP-PA) test. The reverse sequence algorithm for syphilis screening starts with a highly sensitive treponemal test (like an EIA or CIA). If reactive, it reflexes to a non-treponemal test (like RPR) to gauge disease activity. When results are discordant (reactive EIA, nonreactive RPR), it is unclear if the patient has early syphilis (RPR not yet positive), a history of treated syphilis (treponemal tests remain positive for life), or a false-positive EIA. Because this patient has no history of treated syphilis, a false-positive EIA must be differentiated from early infection. The CDC mandates running a second, different treponemal test (such as TP-PA) to resolve this discordance. If the TP-PA is reactive, the patient has syphilis and requires treatment; if nonreactive, the initial EIA was a false positive.

Step-by-Step Solution

1
Identify the screening algorithm being used.
The clinic uses the reverse sequence algorithm (treponemal test first, followed by a non-treponemal test).
Understanding the algorithm is necessary to interpret the sequence of laboratory results.
2
Interpret the specific laboratory results provided in the vignette.
The initial EIA (treponemal) is reactive, but the reflex RPR (non-treponemal) is nonreactive. This is a discordant result.
Discordant results in the reverse algorithm require further investigation because they can represent early primary syphilis, previously treated syphilis, or a false-positive EIA.
3
Determine the guideline-directed next step for discordant reverse sequence results.
The CDC recommends performing a second, different treponemal test (like TP-PA) to confirm if the initial EIA was a true positive or a false positive.
If the TP-PA is nonreactive, the EIA was a false positive, and no treatment is needed. If the TP-PA is reactive, the patient has syphilis (either early or latent) and requires treatment since he has no history of prior therapy.

Key Concept

In the reverse sequence algorithm for syphilis screening, a reactive treponemal test (EIA/CIA) followed by a nonreactive non-treponemal test (RPR/VDRL) must be followed by a second, different treponemal test (TP-PA) to rule out a false-positive initial result.
Estimated Time:1m 30s
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Topics

Infectious Diseases

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